tbuckley/cabot-search huggingface dataset:
Sex Differences in the Recognition, Monitoring, and Management of CKD in Health Care: An Observational Cohort Study
Authors: Oskar Swartling, Yuanhang Yang, Catherine M. Clase, Edouard L. Fu, Manfred Hecking, Sebastian Hödlmoser, Ylva Trolle-Lagerros, Marie Evans, Juan J. Carrero
Journal: Journal of the American Society of Nephrology (2022)

Reported sex differences in the etiology, population prevalence, progression rates, and health outcomes of people with CKD may be explained by differences in health care.We evaluated sex as the variable of interest in a health care-based study of adults (n=227,847) with at least one outpatient eGFR<60 ml/min per 1.73 m2 measurement denoting probable CKD in Stockholm from 2009 to 2017. We calculated the odds ratios for diagnosis of CKD and provision of RASi and statins at inclusion, and hazard ratios for CKD diagnosis, visiting a nephrologist, or monitoring creatinine and albuminuria during follow-up.We identified 227,847 subjects, of whom 126,289 were women (55%). At inclusion, women had lower odds of having received a diagnostic code for CKD and were less likely to have received RASi and statins, despite having guideline-recommended indications. In time-to-event analyses, women were less likely to have received a CKD diagnosis (HR, 0.43; 95% CI, 0.42 to 0.45) and visited a nephrologist (HR, 0.46; 95% CI, 0.43 to 0.48) regardless of disease severity, presence of albuminuria, or criteria for referral. Women were also less likely to undergo monitoring of creatinine or albuminuria, including those with diabetes or hypertension. These differences remained after adjustment for comorbidities, albuminuria, and highest educational achievement, and among subjects with confirmed CKD at retesting. Although in absolute terms all nephrology-care indicators gradually improved over time, the observed sex gap persisted.There were profound sex differences in the detection, recognition, monitoring, referrals, and management of CKD. The disparity was also observed in people at high risk and among those who had guideline-recommended indications.This article contains a podcast at https://www.asn-online.org/media/podcast/JASN/2022_10_11_JASN2022030373.mp3.
HIV: Pandemic disruption and resource cuts have slowed progress, UN report finds
Authors: Jacqui Thornton
Journal: BMJ (2022)

<h3>Abstract</h3> <h3>Aims</h3> The SARS-Cov2 virus binds to the ACE2 receptor for cell entry. It has been suggested that ACE-inhibitors (ACEi) and Angiotensin-2 Blockers (ARB), which are commonly used in patients with hypertension or diabetes and may raise ACE2 levels, could increase the risk of severe COVID19 infection. <h3>Methods and Results</h3> We evaluated this hypothesis in a consecutive cohort of 1200 acute inpatients with COVID19 at two hospitals with a multi-ethnic catchment population in London (UK). The mean age was 68±17 years (57% male) and 74% of patients had at least 1 comorbidity. 415 patients (34.6%) reached the primary endpoint of death or transfer to a critical care unit for organ support within 21-days of symptom onset. 399 patients (33.3 %) were taking ACEi or ARB. Patients on ACEi/ARB were significantly older and had more comorbidities. The odds ratio (OR) for the primary endpoint in patients on ACEi and ARB, after adjustment for age, sex and co-morbidities, was 0.63 (CI 0.47-0.84, p&lt;0.01). <h3>Conclusions</h3> There was no evidence for increased severity of COVID19 disease in hospitalised patients on chronic treatment with ACEi or ARB. A trend towards a beneficial effect of ACEi/ARB requires further evaluation in larger meta-analyses and randomised clinical trials.
Aquatic Federation’s new eligibility policy—an unacceptable erosion of bodily autonomy for women and girls
Authors: Sheree Bekker
Journal: BMJ (2022)

On 20 June 2022, the international federation for aquatic sports (FINA) implemented a new "Policy on eligibility for the men's and women's competition categories." 1 This policy exists "to establish eligibility criteria to regulate the participation of transgender and 46 XY DSD (differences of sex development) athletes in the men's and women's categories in aquatic sports," FINA says. 1 To fulfil this, however, the policy requires that all athletes undergo a test to "certify their chromosomal sex." 1 Additionally, FINA reserves the right to undertake further medical assessment for the purposes of category eligibility where the federation deems it necessary.
Errors in a Study Measure Definition
Journal: JAMA Network Open (2022)

The Original Investigation titled "Use of Medication for Opioid Use Disorder Among US Adolescents and Adults With Need for Opioid Treatment, 2019," 1 published March 23, 2022, has been corrected to fix the definition of a study measure.Wherever past-year criminal legal system contact was indicated, it now reflects lifetime criminal legal system contact.Changes were made in the Abstract, Key Points, Methods section, Results section, and Figure title.This article has been corrected.
Metabolic control by the microbiome
Authors: Timothy O Cox, Patrick Lundgren, Kirti Nath, Christoph A Thaiss
Journal: Genome Medicine (2022)

The interaction between the metabolic activities of the intestinal microbiome and its host forms an important part of health. The basis of this interaction is in part mediated by the release of microbially-derived metabolites that enter the circulation. These products of microbial metabolism thereby interface with the immune, metabolic, or nervous systems of the host to influence physiology. Here, we review the interactions between the metabolic activities of the microbiome and the systemic metabolism of the host. The concept that the endocrine system includes more than just the eukaryotic host component enables the rational design of exogenous interventions that shape human metabolism. An improved mechanistic understanding of the metabolic microbiome-host interaction may therefore pioneer actionable microbiota-based diagnostics or therapeutics that allow the control of host systemic metabolism via the microbiome.
X-CAP improves pathogenicity prediction of stopgain variants
Authors: Ruchir Rastogi, Peter D. Stenson, David N. Cooper, Gill Bejerano
Journal: Genome Medicine (2022)

Abstract Stopgain substitutions are the third-largest class of monogenic human disease mutations and often examined first in patient exomes. Existing computational stopgain pathogenicity predictors, however, exhibit poor performance at the high sensitivity required for clinical use. Here, we introduce a new classifier, termed X-CAP, which uses a novel training methodology and unique feature set to improve the AUROC by 18% and decrease the false-positive rate 4-fold on large variant databases. In patient exomes, X-CAP prioritizes causal stopgains better than existing methods do, further illustrating its clinical utility. X-CAP is available at https://github.com/bejerano-lab/X-CAP .
Trends in Utilization of Electronic Consultations Associated With Patient Payer and Language Among US Academic Medical Centers During the COVID-19 Pandemic
Authors: Anita Arora, Renee Fekieta, Zakia Nouri, Danielle Carder, Megan M. Colgan, Anne Fuhlbrigge, Sara L. Jackson, Samuel Collins, Nathaniel Gleason, Julia Chen
Journal: JAMA Network Open (2022)

Electronic consultations (eConsultations) are increasingly used to obtain specialist guidance, avoiding unnecessary face-to-face patient visits for certain clinical questions. During the COVID-19 pandemic, when in-person care was limited, eConsultations may have helped clinicians obtain specialist input to guide patient care.To understand how the use of eConsultations changed during the COVID-19 pandemic and whether trends in eConsultation utilization differed based on patient's payer and primary language.This retrospective cohort study was conducted at 6 academic medical centers in the United States, all participating in the Association of American Colleges Coordinating Optimal Referral Experiences program. Participants included adult patients who had an outpatient visit, referral, or eConsultation during the study period. Data were analyzed from June 4, 2019, to July 28, 2020.The primary outcome was the eConsultation proportion of specialty contact, defined as the number of completed eConsultations divided by the sum of the number of completed eConsultations and specialty referrals, expressed as a percentage. eConsultation percentages of specialty contact were further stratified by payer type and language. Payers included commercial, Medicare, Medicaid, self-pay or uninsured, and other. Primary language included English and non-English languages.A total of 14 545 completed eConsultations and 189 776 referrals were included. More eConsultations were completed for English-speaking patients (11 363 eConsultations [95.0%]) than non-English-speaking patients (597 eConsultations [5.0%]). Patients with commercial insurance represented the highest number of completed eConsultations (8848 eConsultations [60.8%]) followed by Medicare (3891 eConsultations [26.8%]), Medicaid (930 eConsultations [6.4%]), other insurance (745 eConsultations [5.1%]), and self-pay or no insurance (131 eConsultations [0.9%]). At the start of the pandemic, across all academic medical centers, the percentage of specialty contact conducted via eConsultation significantly increased by 6.21% (95% CI, 4.97%-7.44%; P < .001). When stratified by payer and language, the percentage of specialty contact conducted via eConsultation significantly increased at the beginning of the pandemic for both English-speaking patients (change, 6.09% (95% CI, 4.82% to 7.37%; P < .001) and non-English-speaking patients (change, 8.48% [95% CI, 5.79% to 11.16%]; P < .001) and for all payers, except self-pay and uninsured patients (change, -0.21% [95% CI, [-1.35% to 0.92%]; P = .70).This retrospective cohort study found that eConsultations provided an accessible mechanism for clinicians to receive specialist input when in-person care was limited.
Serum Protein-Induced Tubular Injury
Authors: W. Charles O’Neill
Journal: Journal of the American Society of Nephrology (2022)

Lidberg et al.1 demonstrate that human serum, but not albumin, elicits changes in human proximal tubular cells in culture and propose that proteins other than albumin are responsible for tubular damage in some types of nephrotic syndrome. However, serum is derived from the clotting of blood and, therefore, contains a host of compounds released from platelets, including cytokines, other inflammatory mediators, and growth factors (not all of which are proteins), that are not normally present or are present at much lower levels in circulating blood. In addition, the serum was allogeneic and could contain antibodies reactive against the cultured cells. Therefore, it is not surprising that allogeneic serum has untoward effects on cultured proximal tubular cells. Although nonselective proteinuria may well contribute to tubular injury in certain causes of nephrotic syndrome, this cannot be concluded from Lidberg et al.'s study. Disclosures W.C. O'Neill reports serving in an advisory or leadership role for Elastrin Therapeutics and Inozyme Pharma; receiving research funding from Fresenius Medical Care Renal Therapies Group and the National Institutes of Health; having consultancy agreements with, and having ownership interest in, Inozyme Pharma; having patents or royalties with UpToDate; and receiving income from educational material related to ultrasonography. Funding None.
Fasting triglycerides are positively associated with cardiovascular mortality risk in people with diabetes
Authors: Yutang Wang, Yan Fang, Dianna J Magliano, Fadi J Charchar, Christopher G Sobey, Grant R Drummond, Jonathan Golledge
Journal: Cardiovascular Research (2022)

We investigated the association of fasting triglycerides with cardiovascular disease (CVD) mortality.
Association of Frailty, Age, Socioeconomic Status, and Type of Surgery With Perioperative Outcomes in Patients Undergoing Noncardiac Surgery
Authors: Kai Yi Wu, Pishoy Gouda, Xiaoming Wang, Michelle M. Graham
Journal: JAMA Network Open (2022)

This cohort study examines the association of Hospital Frailty Risk Score classification, demographic characteristics, and type of surgery with risk of mortality among patients undergoing noncardiac surgery.
Hepcidin and Iron in Health and Disease
Authors: Elizabeta Nemeth, Tomas Ganz
Journal: Annual Review of Medicine (2022)

Hepcidin, the iron-regulatory hormone, determines plasma iron concentrations and total body iron content. Hepcidin, secreted by hepatocytes, functions by controlling the activity of the cellular iron exporter ferroportin, which delivers iron to plasma from intestinal iron absorption and from iron stores. Hepcidin concentration in plasma is increased by iron loading and inflammation and is suppressed by erythropoietic stimulation and during pregnancy. Hepcidin deficiency causes iron overload in hemochromatosis and anemias with ineffective erythropoiesis. Hepcidin excess causes iron-restrictive anemias including anemia of inflammation. The development of hepcidin diagnostics and therapeutic agonists and antagonists should improve the treatment of iron disorders.
Silhouette images enable estimation of body fat distribution and associated cardiometabolic risk
Authors: Marcus D. R. Klarqvist, Saaket Agrawal, Nathaniel Diamant, Patrick T. Ellinor, Anthony Philippakis, Kenney Ng, Puneet Batra, Amit V. Khera
Journal: npj Digital Medicine (2022)

Abstract Inter-individual variation in fat distribution is increasingly recognized as clinically important but is not routinely assessed in clinical practice, in part because medical imaging has not been practical to deploy at scale for this task. Here, we report a deep learning model trained on an individual’s body shape outline—or “silhouette” —that enables accurate estimation of specific fat depots of interest, including visceral (VAT), abdominal subcutaneous (ASAT), and gluteofemoral (GFAT) adipose tissue volumes, and VAT/ASAT ratio. Two-dimensional coronal and sagittal silhouettes are constructed from whole-body magnetic resonance images in 40,032 participants of the UK Biobank and used as inputs for a convolutional neural network to predict each of these quantities. Mean age of the study participants is 65 years and 51% are female. A cross-validated deep learning model trained on silhouettes enables accurate estimation of VAT, ASAT, and GFAT volumes ( R 2 : 0.88, 0.93, and 0.93, respectively), outperforming a comparator model combining anthropometric and bioimpedance measures (Δ R 2 = 0.05–0.13). Next, we study VAT/ASAT ratio, a nearly body-mass index (BMI)—and waist circumference-independent marker of metabolically unhealthy fat distribution. While the comparator model poorly predicts VAT/ASAT ratio ( R 2 : 0.17–0.26), a silhouette-based model enables significant improvement ( R 2 : 0.50–0.55). Increased silhouette-predicted VAT/ASAT ratio is associated with increased risk of prevalent and incident type 2 diabetes and coronary artery disease independent of BMI and waist circumference. These results demonstrate that body silhouette images can estimate important measures of fat distribution, laying the scientific foundation for scalable population-based assessment.
Robust boron nanoplatform provokes potent tumoricidal activities via inhibiting heat shock protein
Authors: Yuying Zhao, Ning Liu, Piaoxue Liu, Taojian Fan, Rui Ma, Huijie Hong, Xiaojia Chen, Zhongjian Xie, Han Zhang, Qi Wang, Tongkai Chen
Journal: Asian Journal of Pharmaceutical Sciences (2022)

Near-infrared (NIR)-light-triggered photothermal therapy (PTT) is a promising treatment for breast cancer. However, its therapeutic efficiency is often compromised due to the heat-induced up-regulation of heat shock proteins, which confer photothermal resistance. To solve this urgent problem, PEGylated two-dimensional boron nanosheets (B-PEG)—which allow both multimodal imaging and photothermal conversion—were loaded with gambogic acid (GA), which can inhibit heat shock protein 90 (Hsp90). Experimental findings indicated that this combination of B-PEG and GA could serve as an integrated drug delivery system for cancer diagnosis and treatment. It could be used to administer mild PTT as well as chemotherapy for breast cancer, provide improved anti-tumor effects, and reduce the toxicity of PTT, all while inhibiting breast cancer growth. This drug delivery system could offer a novel tool for administering chemotherapy combined with PTT while avoiding the adverse effects of traditional PTT.
C-arm positioning for standard projections during spinal implant placement
Authors: Lisa Kausch, Sarina Thomas, Holger Kunze, Tobias Norajitra, André Klein, Leonardo Ayala, Jan El Barbari, Eric Mandelka, Maxim Privalov, Sven Vetter, Andreas Mahnken, Lena Maier-Hein, Klaus Maier-Hein
Journal: Medical Image Analysis (2022)

Fluoroscopy-guided trauma and orthopedic surgeries involve the repeated acquisition of correct anatomy-specific standard projections for guidance, monitoring, and evaluating the surgical result. C-arm positioning is usually performed by hand, involving repeated or even continuous fluoroscopy at a cost of radiation exposure and time. We propose to automate this procedure and estimate the pose update for C-arm repositioning directly from a first X-ray without the need for a patient-specific computed tomography scan (CT) or additional technical equipment. Our method is trained on digitally reconstructed radiographs (DRRs) which uniquely provide ground truth labels for an arbitrary number of training examples. The simulated images are complemented with automatically generated segmentations, landmarks, and with simulated k-wires and screws. To successfully achieve a transfer from simulated to real X-rays, and also to increase the interpretability of results, the pipeline was designed to closely reflect the actual clinical decision-making process followed by spinal neurosurgeons. It explicitly incorporates steps such as region-of-interest (ROI) localization, detection of relevant and view-independent landmarks, and subsequent pose regression. The method was validated on a large human cadaver study simulating a real clinical scenario, including k-wires and screws. The proposed procedure obtained superior C-arm positioning accuracy of dθ=8.8°±4.2° average improvement (pt-test≪0.01), robustness, and generalization capabilities compared to the state-of-the-art direct pose regression framework.
An analysis of Neisseria meningitidis strains causing meningococcal septic arthritis in England and Wales: 2010–2020
Authors: George Gyamfi-Brobbey, Stephen A. Clark, Helen Campbell, Aiswarya Lekshmi, Sonia Ribeiro, Andrew Walker, Anna Mensah, Laura Willerton, Lloyd Walsh, Jay Lucidarme, Xilian Bai, Shamez N Ladhani, Saad Ahmed, Tom Walton, Ray Borrow
Journal: Journal of Infection (2022)

To analyze clinical meningococcal strains associated with meningococcal septic arthritis cases in England and Wales, and to identify associations between patient age, the synovial joint affected and strain characteristics.IMD cases confirmed by the Meningococcal Reference Unit (UK Health Security Agency) between January 2010 and December 2020 were included in the analysis. Septic arthritis cases were defined as those featuring detection and/or isolation of N. meningitidis from an articular site. Capsular grouping was performed by serology on clinical isolates and/or real-time PCR on clinical samples.We identified 162 cases of meningococcal septic arthritis, representing 2% of all invasive meningococcal disease cases during the study period. The knee and the hip were the most commonly affected joints, with the former significantly more frequent in adults and the latter seen more commonly in children and adolescents. Group B strains were between 2 and 6 times less likely to cause septic arthritis in relation to groups W, C and Y strains.Meningococcal septic arthritis remains a rare manifestation of invasive meningococcal disease. Strain and age associations identified in this study remain unexplained. Future analyzes including clinical case information may help to explain these findings.
Safety and efficacy of tirzepatide as an add-on to single oral antihyperglycaemic medication in patients with type 2 diabetes in Japan (SURPASS J-combo): a multicentre, randomised, open-label, parallel-group, phase 3 trial
Authors: Takashi Kadowaki, Rina Chin, Akichika Ozeki, Takeshi Imaoka, Yoshihiro Ogawa
Journal: The Lancet Diabetes & Endocrinology (2022)
Cellular and subcellular interactions of graphene-based materials with cancerous and non-cancerous cells
Authors: Shadi Rahimi, Yanyan Chen, Mohsen Zareian, Santosh Pandit, Ivan Mijakovic
Journal: Advanced Drug Delivery Reviews (2022)

Despite significant advances in early detection and personalized treatment, cancer is still among the leading causes of death globally. One of the possible anticancer approaches that is presently receiving a lot of attention is the development of nanocarriers capable of specific and efficient delivery of anticancer drugs. Graphene-based materials are promising nanocarriers in this respect, due to their high drug loading capacity and biocompatibility. In this review, we present an overview on the interactions of graphene-based materials with normal mammalian cells at the molecular level as well as cellular and subcellular levels, including plasma membrane, cytoskeleton, and membrane-bound organelles such as lysosomes, mitochondria, nucleus, endoplasmic reticulum, and peroxisome. In parallel, we assemble the knowledge about the interactions of graphene-based materials with cancerous cells, that are considered as the potential applications of these materials for cancer therapy including metastasis treatment, targeted drug delivery, and differentiation to non-cancer stem cells. We highlight the influence of key parameters, such as the size and surface chemistry of graphene-based materials that govern the efficiency of internalization and biocompatibility of these particles in vitro and in vivo. Finally, this review aims to correlate the key parameters of graphene-based nanomaterials specially graphene oxide, such as size and surface modifications, to their interactions with the cancerous and non-cancerous cells for designing and engineering them for bio-applications and especially for therapeutic purposes.
Peculiar Variations of the Electrostatic Potential of Spike Protein N-terminal Domain Associated with the Emergence of Successive SARS-CoV-2 Omicron Lineages
Authors: Stefano Pascarella, Massimo Ciccozzi, Domenico Benvenuto, Alessandra Borsetti, Roberto Cauda, Antonio Cassone
Journal: Journal of Infection (2022)